Interleukin-19 Impairment in Active Crohn's Disease Patients
Por:
Canto, E, Planella, EG, Zamora-Atenza, C, Nieto, JC, Gordillo, J, Ortiz, MA, Meton, I, Serrano, E, Vegas, E, Garcia-Bosch, O, Juarez, C, Vidal, S
Publicada:
9 abr 2014
Resumen:
The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNF alpha and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p< 0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNF alpha production in PBMC (850.7 +/- 75.29 pg/ml vs 2626.0 +/- 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 +/- 1.55% vs 13.98 +/- 2.05%; p<0.05) and IL-4 production (32.5 +/- 8.9 pg/ml vs 13.5 +/- 2.9 pg/ml; p< 0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.
Filiaciones:
Canto, E:
IIB St Pau, Biomed Res Inst St Pau, Dept Immunol, Barcelona, Spain
Planella, EG:
Hosp Santa Creu & Sant Pau, Dept Digest Pathol, Barcelona, Spain
Zamora-Atenza, C:
IIB St Pau, Biomed Res Inst St Pau, Dept Immunol, Barcelona, Spain
Nieto, JC:
IIB St Pau, Biomed Res Inst St Pau, Dept Immunol, Barcelona, Spain
Gordillo, J:
Hosp Santa Creu & Sant Pau, Dept Digest Pathol, Barcelona, Spain
Ortiz, MA:
IIB St Pau, Biomed Res Inst St Pau, Dept Immunol, Barcelona, Spain
Meton, I:
Univ Barcelona, Fac Pharm, Dept Biochem & Mol Biol, Barcelona, Spain
Serrano, E:
IIB St Pau, Biomed Res Inst St Pau, PSCT Platforms, Barcelona, Spain
Vegas, E:
Univ Barcelona, Fac Biol, Dept Stat, Barcelona, Spain
Garcia-Bosch, O:
Hosp St Joan Despi Moises Broggi, Dept Digest, Barcelona, Spain
Juarez, C:
Hosp Santa Creu & Sant Pau, Dept Immunol, Barcelona, Spain
Univ Autonoma Barcelona, E-08193 Barcelona, Spain
Vidal, S:
IIB St Pau, Biomed Res Inst St Pau, Dept Immunol, Barcelona, Spain
Univ Autonoma Barcelona, E-08193 Barcelona, Spain
Gold, Green Published
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